Percutaneous absorption and metabolism of aldrin by rat skin in diffusion cells

Macpherson, Sara E.; Scott, Robert C.; Williams, Faith M.

doi:10.1007/bf01973723

Cited by 11 publications

(5 citation statements)

References 7 publications

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“…According to this paper, more than 99% of the epoxidation product, dieldrin, was probably formed locally by dermal metabolism of percutaneously absorbed aldrin. Other papers detecting the metabolism of aldrin to dieldrin by rat skin have also been published in the literature ( , ).…”

Section: Resultsmentioning

confidence: 99%

Computer-Aided Knowledge Generation for Understanding Skin Sensitization Mechanisms: The TOPS-MODE Approach

Estrada

Patlewicz

Chamberlain

et al. 2003

Chem. Res. Toxicol.

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The TOPS-MODE (topological substructural molecular descriptors) approach is used to derive models for understanding the molecular structural contribution to skin sensitization. A data set of 93 compounds was used in the development of the models; 29 new skin sensitization values (EC3) are reported here for the first time. The models developed possess high predictivity and have been validated through the use of cross-validation and external validation sets. The models have enabled the formulation of potential new structural alerts far faster and using less data than typically required by traditional approaches. Structural contributions to skin sensitization for various classes of chemicals are presented on the basis of bond contributions. The models have also been able to identify potential structural alerts for chemicals requiring metabolic activation.

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Section: Resultsmentioning

confidence: 99%

Computer-Aided Knowledge Generation for Understanding Skin Sensitization Mechanisms: The TOPS-MODE Approach

Estrada

Patlewicz

Chamberlain

et al. 2003

Chem. Res. Toxicol.

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“…Using a rat epidermal membrane, carbaryl applied at 200 nmol cm-2 was absorbed to ethanol/water as receptor fluid; 10% in 5 h. This absorption relates to the recovery observed here of 2.76% through whole rat skin to ethanol/water receptor fluid in 7.5 h. Recovery to receptor fluid was lower with aqueous receptors, but previous work has shown that with saline and Earles MEM tissue culture medium as the receptor fluids, drug metabolising enzymes are relatively well supported within the skin for several hours, although in the presence of 50% ethanol/water the enzyme activity falls off very rapidly (Macpherson et al 1990). These conditions have been shown to support metabolism of aldrin to dieldrin during absorption through the skin (Macpherson et al 1991). Therefore the capacity for carbaryl metabolism was present when aqueous receptors were used, supporting the assumption that insufficient chemical came in contact with the enzymes for metabolism to be detected.…”

Section: Discussionmentioning

confidence: 86%

Fate of carbaryl in rat skin

Macpherson¹,

Scott²,

Williams

1991

Arch Toxicol

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Metabolism of carbaryl by rat liver and skin post-mitochondrial fraction has been measured in the presence and absence of cofactors to promote different metabolic pathways. The metabolic capacity was compared with the metabolism of carbaryl during percutaneous absorption in a static skin diffusion system using a variety of receptor fluids. Carbaryl was metabolised by hydrolysis, and ring hydroxylation followed by conjugation to the glucuronide or sulphate with liver post-mitochondrial fraction. Using skin post-mitochondrial fraction only hydrolysis and conjugation were detected. No metabolism was seen during percutaneous absorption in vitro even with receptor fluids which maintain the skin tissue viability. Studies using post-mitochondrial fraction indicate the metabolic capacity of the tissue, whereas during absorption, rates of absorption and accessibility of substrate to the metabolising enzymes must be considered.

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“…27 The choice of a suitable receptor solution can also be compromised by a need to maintain skin viability. 19 Macpherson et al 30 have reported that the pesticide aldrin is absorbed through skin into ethanol-water but not aqueous receptor fluids. However, skin viability was not supported by an ethanol-water system.…”

Section: Discussionmentioning

confidence: 99%

Diffusion modeling of percutaneous absorption kinetics. 1. Effects of flow rate, receptor sampling rate, and viable epidermal resistance for a constant donor concentration

Anissimov

Roberts

1999

Journal of Pharmaceutical Sciences

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A diffusion model for the percutaneous absorption of a solute through the skin is developed for the specific case of a constant donor concentration with a finite removal rate from the receptor due to either perfusion rate or sampling. The model has been developed to include a viable epidermal resistance and a donor-stratum corneum interfacial resistance. Numerical inversion of the Laplace domain solutions were used for simulations of solute flux and cumulative amount absorbed and to model specific examples of percutaneous absorption. Limits of the Laplace domain solutions were used to define the steady-state flux, lag time, and receptor concentration. Steady-state approximations obtained from the solutions were used to relate the steady-state flux and the effective permeability coefficient to the viable epidermis resistance, a donor-stratum corneum interfacial resistance, receptor removal rate, and partitioning between the receptor and donor phases. The lag time was shown to be dependent on these parameters and on the volume of the receptor phase. It is concluded that curvilinear cumulative amount and flux-time profiles are dependent on the processes affecting percutaneous absorption, the shapes of the profiles reflecting the processes most determining transport.

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Percutaneous absorption and metabolism of aldrin by rat skin in diffusion cells

Cited by 11 publications

References 7 publications

Computer-Aided Knowledge Generation for Understanding Skin Sensitization Mechanisms: The TOPS-MODE Approach

Computer-Aided Knowledge Generation for Understanding Skin Sensitization Mechanisms: The TOPS-MODE Approach

Fate of carbaryl in rat skin

Diffusion modeling of percutaneous absorption kinetics. 1. Effects of flow rate, receptor sampling rate, and viable epidermal resistance for a constant donor concentration

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